Duration of activity of the acid, methyl ester and amide of an orally active platelet aggregation inhibitory prostanoid in the rat

• Published in: Prostaglandins Vol. 19; no. 1; pp. 139 - 153
• Main Authors: Honohan, Thomas, Nishizawa, Edward E., Douglas, Scott L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 1980
• Subjects: Adenosine Diphosphate - pharmacology; Administration, Oral; Animals; Duodenum; Injections; Injections, Intravenous; Male; Platelet Aggregation - drug effects; Prostaglandins E, Synthetic - administration & dosage; Rats
• ISSN: 0090-6980
• DOI: 10.1016/0090-6980(80)90161-6

The prostanoid 3-oxa-4,5,6-trinor-3,7-inter- m -phenylene PGE 1 (OI-PGE 1) has been shown to be a more potent inhibitor of ADP-induced human platelet aggregation than PGE 1. OI-PGE 1 inhibits ex vivo ADP-induced platelet aggregation for 60 minutes after an oral dose of 20 mg/kg to rats. Present studies compare duration of ex vivo inhibition to ADP-induced platelet aggregation in the rat by OI-PGE 1, its methyl ester and amide after administration by various routes. All oral (p.o.) and intraduodenal (i.d.) doses were 20 mg/kg and all intravenous (i.v.) doses were 1 mg/kg. OI-PGE 1 and its methyl ester had the same duration of activity after i.v. (60 min.) and p.o. (60 min.) administration, however, the methyl ester, when administered i.d., had a longer duration of activity than the free acid i.d. (>90 min. vs. 60 min.). OI-PGE 1-amide had significantly longer duration than the acid or methyl ester after i.v. (>120 min.), p.o. (>240 min.) or i.d. (>240 min.) administration. Present data suggest that in the rat (1) intestinal absorption of OI-PGE 1-methyl ester is more efficient than it is for the free acid and (2) due to metabolic and/or distributional differences between OI-PGE 1 and its amide, the amide has a much greater duration of activity.